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To better understand the latter, we stimulated human macrophages in vitro with TLR ligands in the presence of high-density immune complexes (IC). This combination of stimuli resulted in a broad suppression of inflammatory mediators and an upregulation of molecules involved in tissue remodeling and angiogenesis. Transcriptomic analysis of TLR stimulation in the presence of IC predicted the downstream activation of AKT and the inhibition of GSK3. Consequently, we pretreated LPS-stimulated human macrophages with small molecule inhibitors of GSK3 to partially phenocopy the regulatory effects of stimulation in the presence of IC. The upregulation of DC-STAMP and matrix metalloproteases was observed on these cells and may represent potential biomarkers for this regulatory activation state. To demonstrate the presence of these anti-inflammatory, growth-promoting macrophages in a human infectious disease, biopsies from patients with leprosy (Hanseniasis) were analyzed. The lepromatous form of this disease is characterized by hypergammaglobulinemia and defective cell-mediated immunity. Lesions in lepromatous leprosy contained macrophages with a regulatory phenotype expressing higher levels of DC-STAMP and lower levels of IL-12, relative to macrophages in tuberculoid leprosy lesions. Therefore, we propose that increased signaling by Fc\u03b3R cross-linking on TLR-stimulated macrophages can paradoxically promote the resolution of inflammation and initiate processes critical to tissue growth and repair. It can also contribute to infectious disease progression.<\/jats:p>","DOI":"10.4049\/jimmunol.1901382","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T21:25:18Z","timestamp":1590009918000},"page":"102-112","source":"Crossref","is-referenced-by-count":15,"title":["Immune Complex\u2013Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity"],"prefix":"10.1093","volume":"205","author":[{"given":"Elizabeth","family":"Dalby","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory, Inflammation, and Autoimmunity , AstraZeneca, Gaithersburg, MD 20878"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kajal","family":"Hamidzadeh","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1343-7255","authenticated-orcid":false,"given":"Prabha","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-9559","authenticated-orcid":false,"given":"V Keith","family":"Hughitt","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742"},{"name":"Center for Bioinformatics and Computational Biology, University of Maryland , College Park, MD 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagner Luiz","family":"Tafuri","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Federal University of Minas Gerais , Belo Horizonte 31270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria Esteves","family":"Arantes","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Federal University of Minas Gerais , Belo Horizonte 31270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael Alves","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Instituto Metropolitano de Ensino Superior , Ipatinga 35164-253 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Herbst","sequence":"additional","affiliation":[{"name":"Department of Respiratory, Inflammation, and Autoimmunity , AstraZeneca, Gaithersburg, MD 20878"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7970-3312","authenticated-orcid":false,"given":"Najib M","family":"El-Sayed","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742"},{"name":"Center for Bioinformatics and Computational Biology, University of Maryland , College Park, MD 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2796-0485","authenticated-orcid":false,"given":"Gary P","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Respiratory, Inflammation, and Autoimmunity , AstraZeneca, Gaithersburg, MD 20878"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-4187","authenticated-orcid":false,"given":"David M","family":"Mosser","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"2025030417503999500_r1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. 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